Study on the Effect of CyPA Antibody Therapy on Bleomycin-induced Systemic Sclerosis in Mice
Objective:To investigate the effects of neutralizing CyPA antibody blocking therapy in course of systemic sclerosis induced by bleomycin(BLM)in mice,and to clarify the effects of neutralizing CyPA antibody on the process of systemic sclerosis in mice.Methods:Bleomycin induced systemic sclerosis model was adopted.The mice were divided into control group,BLM group,early treatment group(CyPA antibody or control IgG was used for treatment on day 1,8,15,22 in the mice model of systemic sclerosis induced by BLM)and late treatment group(CyPA antibody or control IgG was used for treatment on day 22 in the mouse model of systemic sclerosis induced by BLM).HE staining and Masson staining were used to observe the skin lesions of mice with systemic sclerosis.The expression levels of α smooth muscle actin(α-SMA),TGF-β,and inflammatory factors CyPA,interleukin 1β(IL-1β),IL-6 in the skin tissues of mice were detected by histochemical staining.The expression levels of serum cytokines including IL-17α,TGF-β,integrin beta 6(ITG-β6),TNF receptor superfamily member 1 1B(TNFRSF1 1b),IL-6,IL-1α,IL-1β,IL-10,TNF,CC-chemokine ligand 5(CCL5),CXC chemokine ligand 9(CXCL9),nicotinamide adenine dinucleotide kinase(NADK),erythropoietin(EPO),colony stimulating factor 2(CSF2)in serum were detected by Olink mouse exploratory panel.Results:Compared with that in the control group,the skin dermis of BLM group was thickened,and the skin collagen increased.The pathological lesions were alleviated in the early treatment group compared with that in the BLM group.Compared with that in the control group,the plasma concentrations of pro-inflammatory factors IL-1β,IL-6,and CyPA in BLM group significantly upregulated.In the early stage of systemic sclerosis,neutralizing CyPA antibody intervention treatment had a significant effect accompanied by decreasing the expression of IL-1β,IL-6,and CyPA,indicating that the inflammation was significantly alleviated.In addition,the expression levels of α-SMA and TGF-β decreased significantly,which illustrated collagen aggregation and tissue lesions were significantly alleviated.Conclusion:In the early stage of inflammation,neutralizing CyPA antibody blocking therapy can effectively alleviate the progression of systemic sclerosis in mice by reducing the secretion of inflammatory cytokines IL-1β and IL-6.
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